Trial Outcomes & Findings for Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia (NCT NCT00728728)

NCT ID: NCT00728728

Last Updated: 2017-02-10

Results Overview

The MATRICS Consensus Cognitive Battery (MCCB) is a standardized battery for use with adults with schizophrenia and related disorders to measure cognition in these individuals. The MCCB consists of ten individually administered test which measure speed of processing, attention/vigilance, nonverbal working memory, verbal working memory, verbal learning, visual learning, reasoning and problem solving and social cognition. The primary raw scores are entered into the MCCB Computer Scoring Program which then generates the corresponding T-scores and percentiles, along with a graphic profile of the scores for each of the seven cognitive domains. Higher scores indicate better performance.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

Results posted on

2017-02-10

Participant Flow

Participant milestones

Participant milestones
Measure
Arm 1: Pregnenolone
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
Placebo control group
Overall Study
STARTED
42
46
Overall Study
COMPLETED
38
34
Overall Study
NOT COMPLETED
4
12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pregnenolone for Cognitive and Negative Symptoms in Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Arm 1: Pregnenolone
n=42 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=46 Participants
Placebo control group
Total
n=88 Participants
Total of all reporting groups
Age, Continuous
51.9 years
STANDARD_DEVIATION 8.5 • n=5 Participants
51.6 years
STANDARD_DEVIATION 8.4 • n=7 Participants
51.7 years
STANDARD_DEVIATION 8.4 • n=5 Participants
Gender
Female
6 Participants
n=5 Participants
7 Participants
n=7 Participants
13 Participants
n=5 Participants
Gender
Male
36 Participants
n=5 Participants
39 Participants
n=7 Participants
75 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
27 Participants
n=5 Participants
36 Participants
n=7 Participants
63 Participants
n=5 Participants
Race (NIH/OMB)
White
12 Participants
n=5 Participants
9 Participants
n=7 Participants
21 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
3 Participants
n=5 Participants
1 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
42 participants
n=5 Participants
46 participants
n=7 Participants
88 participants
n=5 Participants

PRIMARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

The MATRICS Consensus Cognitive Battery (MCCB) is a standardized battery for use with adults with schizophrenia and related disorders to measure cognition in these individuals. The MCCB consists of ten individually administered test which measure speed of processing, attention/vigilance, nonverbal working memory, verbal working memory, verbal learning, visual learning, reasoning and problem solving and social cognition. The primary raw scores are entered into the MCCB Computer Scoring Program which then generates the corresponding T-scores and percentiles, along with a graphic profile of the scores for each of the seven cognitive domains. Higher scores indicate better performance.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
MATRICS Consensus Cognitive Battery (MCCB)
Baseline
30.92 T score
Standard Error 1.83
30.32 T score
Standard Error 1.40
MATRICS Consensus Cognitive Battery (MCCB)
Week 4
33.43 T score
Standard Error 1.75
32.76 T score
Standard Error 1.72
MATRICS Consensus Cognitive Battery (MCCB)
Week 8
36.97 T score
Standard Error 1.90
34.25 T score
Standard Error 2.11

PRIMARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional Capacity and assesses skills involved in community tasks. It is composed of five subdomains (comprehension and planning, finance, communication, mobility and house management) when combined, measures functional capacity. The comprehension and planning subdomain ranges from 0 to 14, the finance subdomain ranges from 0 to 11, the communication subdomain ranges from 0 to 12, the mobility subdomain ranges from 0 to 9, and the house management subdomain ranges from 0 to 4. Then a medication management score of 0 to 37 is added. In total, the Assessment is thus scored on a 0 to 87 scale, with higher scores indicating better performance.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
University of California Performance-based Skills Assessment (UPSA)
Baseline
77.49 total score
Standard Error 1.63
76.68 total score
Standard Error 1.76
University of California Performance-based Skills Assessment (UPSA)
Week 4
77.29 total score
Standard Error 2.65
80.12 total score
Standard Error 1.63
University of California Performance-based Skills Assessment (UPSA)
Week 8
85.63 total score
Standard Error 1.31
82.03 total score
Standard Error 2.05

PRIMARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The domains of cognitive function assessed and the associated tests include: Verbal Memory \& Learning (Verbal Memory), Working Memory (Digit Sequencing), Motor Function (Token Motor Task), Verbal Fluency (Semantic and Letter Fluency), Speed of Processing (Symbol Coding), and Executive Function (Tower of London). These domains are then converted to Z scores compared to standardized scoring scales, with higher scores representing better performance.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
Brief Assessment of Cognition in Schizophrenia (BACS)
Baseline
-1.37 Z score
Standard Error 0.13
-1.53 Z score
Standard Error 0.12
Brief Assessment of Cognition in Schizophrenia (BACS)
Week 4
-1.11 Z score
Standard Error 0.14
-1.17 Z score
Standard Error 0.12
Brief Assessment of Cognition in Schizophrenia (BACS)
Week 8
-0.79 Z score
Standard Error 0.13
-1.09 Z score
Standard Error 0.18

PRIMARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

The Scale for the Assessment of Negative Symptoms (SANS) is an assessment used to obtain clinical ratings of negative symptoms in patients with schizophrenia. The SANS assesses five symptom complexes. They are: affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. 24 assessments are conducted on a six-point scale (0=not at all to 5=severe) each, for a total scoring range of 0-120. Lower scores represent better performance.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
Scale for the Assessment of Negative Symptoms(SANS)
Baseline
26.92 total score
Standard Error 1.75
25.88 total score
Standard Error 1.94
Scale for the Assessment of Negative Symptoms(SANS)
Week 4
23.87 total score
Standard Error 2.05
21.74 total score
Standard Error 1.87
Scale for the Assessment of Negative Symptoms(SANS)
Week 8
21.00 total score
Standard Error 2.47
20.77 total score
Standard Error 2.40

SECONDARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period.

The CDSS assesses the level of depression in schizophrenia by measuring nine items on a 0 (absent) to 3 (severe) scale each. Thus, the total score range is 0 to 27. Lower scores represent better outcomes.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
The Calgary Depression Scale for Schizophrenia (CDSS)
Baseline
2.84 total score
Standard Error 0.64
3.18 total score
Standard Error 0.64
The Calgary Depression Scale for Schizophrenia (CDSS)
Week 4
2.39 total score
Standard Error 0.62
2.79 total score
Standard Error 0.66
The Calgary Depression Scale for Schizophrenia (CDSS)
Week 8
2.68 total score
Standard Error 0.74
2.46 total score
Standard Error 0.90

SECONDARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

The PANSS measures positive and negative symptoms of schizophrenia through administering a structured interview. After the interview, 25 PANSS items are each rated 1 (absent) to 7 (extreme). These items are organized into five scales: Negative, Positive, Dysphoric Mood, Activation, and Autistic Preoccupation. The combination of the 25 items produces a total score range of 25-175, and lower scores represent better outcomes.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=38 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=34 Participants
Placebo control group
Positive and Negative Syndrome Scale (PANSS)
Baseline
65.74 total score
Standard Error 2.28
63.68 total score
Standard Error 2.58
Positive and Negative Syndrome Scale (PANSS)
Week 4
61.47 total score
Standard Error 2.55
56.79 total score
Standard Error 2.03
Positive and Negative Syndrome Scale (PANSS)
Week 8
59.10 total score
Standard Error 2.95
57.12 total score
Standard Error 3.16

SECONDARY outcome

Timeframe: Prospective, outcome measures collected over 10 week trial period. (Weeks 2, 6 and 10)

Population: Missing data for a total of 5 participants for the CGI.

The CGI scale provides a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication. The CGI comprises two companion one-item measures evaluating the severity of psychopathology from 1 to 7 and change from the initiation of treatment on a similar seven-point scale. Thus, scores range from 2 to 14, with lower scores representing better outcomes.

Outcome measures

Outcome measures
Measure
Arm 1: Pregnenolone
n=34 Participants
Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=33 Participants
Placebo control group
Clinical Global Impressions (CGI) Scale
Baseline
3.56 score
Standard Error 0.15
3.58 score
Standard Error 0.13
Clinical Global Impressions (CGI) Scale
Week 4
3.39 score
Standard Error 0.12
3.39 score
Standard Error 0.14
Clinical Global Impressions (CGI) Scale
Week 8
3.42 score
Standard Error 0.12
3.24 score
Standard Error 0.17

Adverse Events

Arm 1: Pregnenolone

Serious events: 3 serious events
Other events: 31 other events
Deaths: 0 deaths

Arm 2: Placebo

Serious events: 4 serious events
Other events: 38 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Arm 1: Pregnenolone
n=42 participants at risk
Pregnenolone Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=46 participants at risk
Placebo Placebo: Placebo
Psychiatric disorders
Psychiatric Hopitalization
4.8%
2/42
4.3%
2/46
Endocrine disorders
Hospitalization for Elevated Glucose
2.4%
1/42
0.00%
0/46
Gastrointestinal disorders
Medical Admission for Observation
0.00%
0/42
2.2%
1/46
Reproductive system and breast disorders
Breast Cancer Diagnosis
0.00%
0/42
2.2%
1/46

Other adverse events

Other adverse events
Measure
Arm 1: Pregnenolone
n=42 participants at risk
Pregnenolone Dietary Supplement: Pregnenolone: Pregnenolone 50mg BID x 14 days, followed by Pregnenolone 150 x 14 days, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial.
Arm 2: Placebo
n=46 participants at risk
Placebo Placebo: Placebo
Nervous system disorders
Drowsiness
26.2%
11/42
21.7%
10/46
Nervous system disorders
Hypersomnia
21.4%
9/42
17.4%
8/46
Gastrointestinal disorders
Diarrhea
19.0%
8/42
15.2%
7/46
Nervous system disorders
Insomnia
16.7%
7/42
6.5%
3/46
Nervous system disorders
Decreased Appetite
19.0%
8/42
13.0%
6/46
Nervous system disorders
Increased appetite
16.7%
7/42
19.6%
9/46
Gastrointestinal disorders
Constipation
11.9%
5/42
26.1%
12/46
Gastrointestinal disorders
Nausea
14.3%
6/42
4.3%
2/46
Nervous system disorders
Dry mouth
11.9%
5/42
17.4%
8/46
Musculoskeletal and connective tissue disorders
Cramps
16.7%
7/42
13.0%
6/46
Nervous system disorders
Headache
14.3%
6/42
19.6%
9/46
Nervous system disorders
Tremor
11.9%
5/42
10.9%
5/46
Nervous system disorders
Increased Salivation
11.9%
5/42
2.2%
1/46
Cardiac disorders
Palpitations
9.5%
4/42
15.2%
7/46
Ear and labyrinth disorders
Tinnitus
7.1%
3/42
10.9%
5/46
Skin and subcutaneous tissue disorders
Dermatological
7.1%
3/42
8.7%
4/46
Musculoskeletal and connective tissue disorders
Joint pain/ stiffness
11.9%
5/42
4.3%
2/46
Nervous system disorders
Dizziness
9.5%
4/42
19.6%
9/46
Nervous system disorders
Sweating
4.8%
2/42
2.2%
1/46
Gastrointestinal disorders
Vomiting
2.4%
1/42
4.3%
2/46
Musculoskeletal and connective tissue disorders
Muscle Pain/Stiffness
7.1%
3/42
8.7%
4/46
Nervous system disorders
Other: "Lucid Dreams"
2.4%
1/42
0.00%
0/46
General disorders
Restlessness
7.1%
3/42
8.7%
4/46
Renal and urinary disorders
Nocturnal/Enuresis
2.4%
1/42
2.2%
1/46
Nervous system disorders
Decreased Interest in Sex
4.8%
2/42
0.00%
0/46
Nervous system disorders
Vertigo
2.4%
1/42
0.00%
0/46
Eye disorders
Blurred Vision
2.4%
1/42
8.7%
4/46
Reproductive system and breast disorders
Menstrual Disturbance
2.4%
1/42
0.00%
0/46
General disorders
Nasal Congestion
2.4%
1/42
8.7%
4/46
General disorders
Peripheral Edema
2.4%
1/42
2.2%
1/46
General disorders
Malaise
2.4%
1/42
2.2%
1/46
Musculoskeletal and connective tissue disorders
Akathisia
2.4%
1/42
0.00%
0/46
Nervous system disorders
Excitement/Agitation
2.4%
1/42
2.2%
1/46
Nervous system disorders
Confusion
2.4%
1/42
4.3%
2/46
Nervous system disorders
Paresthesia
0.00%
0/42
4.3%
2/46
Cardiac disorders
Tachycardia
0.00%
0/42
2.2%
1/46
Musculoskeletal and connective tissue disorders
Increased Motor Activity
0.00%
0/42
2.2%
1/46
Blood and lymphatic system disorders
Cold Extremities
0.00%
0/42
2.2%
1/46
Renal and urinary disorders
Other: "Urinary Retention"
0.00%
0/42
2.2%
1/46
Musculoskeletal and connective tissue disorders
Other: "Head/Neck Twitching"
0.00%
0/42
2.2%
1/46

Additional Information

Christine E. Marx, MD

VHA Durham

Phone: 9192860411

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place